After the demolition of the city walls, the properties in Karlín were counted among the cheapest properties of Prague. For that reason, the number of industrial enterprises and dwellings grew very quickly in the area of "Rohan Island" (Rohanský ostrov). On January 1, 1922, Karlín was incorporated into Prague. At this time, the electrical engineering pioneer and industrialist František Křižík had great influence in the area. He established a streetcar line, which he then sold to the city.

In the 1970s, traffic was derouted onto the Rohanské nábřeží and the main arterial road was relieved. Since 1990 Karlín is connected to the Prague Metro and a pedestrian zone has been established. In 2002 Karlín was severely affected by the 100-year flood. It has since recovered and is becoming a new destination for businesses and residences.

A notable building in Karlín is the Karlín Railway Bridge, which connects the main railway station to the Bubny station. The viaduct (also called Karlín viaduct) was named after Alois Negrelli, it is 1,111 m long and was put into operation on June 1 1850. It is the longest bridge/viaduct on Czech territory.